Data collection apparatus for attachment to an injection device

ABSTRACT

A data collection device comprises: a first portion having one or more features configured for attaching of the first portion to a dosage knob of an injection device; a second portion rotatably coupled with the first portion, wherein at least part of the second portion is movable axially relative to the first portion; a sensor arrangement configured to detect rotation of the first portion relative to the second portion; and a processor arrangement configured to, based on said detected movement, determine a medicament amount expelled by the injection device, wherein the coupling arrangement is configured to provide a non-permanent coupling between the first portion and the dosage knob of the injection device.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. application Ser. No.16/742,219, filed Jan. 14, 2020, which is a continuation of U.S.application Ser. No. 15/579,656, filed Dec. 5, 2017, which is the U.S.national stage entry under 35 USC § 371 of International PatentApplication No. PCT/EP2016/063139, filed on Jun. 9, 2016, which claimspriority to European Patent Application No. 15171252.8, filed on Jun. 9,2015, and European Patent Application No. 15199308.6, filed on Dec. 10,2015, the entire contents of all of which are incorporated herein byreference.

TECHNICAL FIELD

The present disclosure generally relates to a data collection device forattachment to an injection device and collecting medicament dosageinformation therefrom.

BACKGROUND

A variety of diseases exists that require regular treatment by injectionof a medicament. Such injection can be performed by using injectiondevices, which are applied either by medical personnel or by patientsthemselves. As an example, type-1 and type-2 diabetes can be treated bypatients themselves by injection of insulin doses, for example once orseveral times per day. For instance, a pre-filled disposable insulin pencan be used as an injection device. Alternatively, a re-usable pen maybe used. A re-usable pen allows replacement of an empty medicamentcartridge by a new one. Either pen may come with a set of one-wayneedles that are replaced before each use. The insulin dose to beinjected can then for instance be manually selected at the insulin penby turning a dosage knob and observing the actual dose from a dosewindow or display of the insulin pen. The dose is then injected byinserting the needle into a suited skin portion and pressing aninjection button of the insulin pen. To be able to monitor insulininjection, for instance to prevent false handling of the insulin pen orto keep track of the doses already applied, it is desirable to measureinformation related to a condition and/or use of the injection device,such as for instance information on the injected insulin dose.

SUMMARY

An aspect of the disclosure provides a data collection device comprisinga first portion configured for attachment to an injection device, asecond portion rotatably attached to the first portion, a sensorarrangement configured to detect rotation of the first portion relativeto the second portion and a processor arrangement configured to, basedon said detected movement, determine a medicament amount expelled by theinjection device.

Since the data collection device does not utilize recognition ofcharacters on the injection device to determine a medicament dosageamount, the data collection device may, optionally, be configured sothat it does not obscure display of a currently programmed dosage,avoiding the need to provide an additional display of the dosage amountfor viewing by the user. In addition, the determination of themedicament dosage amount may be less computationally intensive thanoptical character recognition techniques.

Additionally, the data collection device may be implemented in anembodiment wherein the second portion comprises an outer portion havingfirst electrical contacts, the second portion comprises an inner portionhaving second electrical contacts and the inner portion is axiallymovable relative to the outer portion to engage said first electricalcontacts with said second electrical contacts when pressure is appliedto the outer portion. For instance, engagement of the first and secondelectrical contacts may activate the data collection device.

Further additionally data collection device may comprise apiezo-electric generator arranged to power the data collection devicewhen pressure is applied to the outer portion.

Additionally and/or alternatively, the data collection device maycomprise a timer triggered when said first electrical contacts areengaged and/or disengaged from the second electrical contacts.

Additionally and/or alternatively, the data collection device may beconfigured to determine an elapsed time since the timer was lasttriggered and to generate an alert if the elapsed time is inconsistentwith a threshold condition.

Additionally and/or alternatively, the data collection device may havethe processor arrangement configured to determine a time stamp for theadministration of the medicament dosage using said timer and to storethe determined medicament dosage and said time stamp.

Additionally and/or alternatively, the data collection device may havethe processor arrangement configured to transmit a log of determinedmedicament dosages and time stamp information to another device.

Additionally and/or alternatively, the data collection device may beconfigured to switch between a first configuration in which rotation ofthe first portion relative to the second portion is prevented and asecond configuration in which the first portion can be rotated relativeto the second portion. For example, the second portion may be axiallymovable relative to the first portion to switch between said firstconfiguration and said second configuration.

Additionally and/or alternatively, the data collection device may havethe sensor arrangement comprising one or more of an optical sensor, amagnetic sensor, a capacitive sensor or a mechanical sensor.

Additionally and/or alternatively, the data collection device may havethe first portion being configured to be attached to a rotatablecomponent of the injection device.

Additionally and/or alternatively, the data collection device maycomprise a transfer arrangement arranged to engage a rotatable componentof the injection device wherein the first portion is configured to beattached to a rotatable component of the injection device and whereinthe transfer arrangement is configured to rotate the first portionrelative to the second portion when said rotatable component rotates.

Additionally and/or alternatively, the data collection device may havethe transfer arrangement comprising a friction wheel.

An aspect of the disclosure provides a medicament administrationapparatus which comprises an injection device having a rotatablecomponent configured to rotate as a medicament is expelled from theinjection device and a data collection device as set out in thepreceding sections.

Additionally and/or alternatively, the medicament administrationapparatus may have the injection device comprising an injection buttonarranged to cause expulsion of the medicament from the injection deviceand may have the second portion being arranged to press on the injectionbutton when pressure is applied to the second portion.

Additionally and/or alternatively, the medicament administrationapparatus may comprise an injection device comprising a rotatablecomponent configured to rotate as a medicament is expelled from theinjection device; and a data collection device as set out above whereinthe transfer arrangement is arranged to engage a rotatable sleeve of theinjection device.

In some embodiments, the injection device is a disposable injectiondevice and the data collection device is configured to be releasablyattachable to the injection device. In some embodiments, the injectiondevice may be a reusable injection device and the data collection devicemay be configured to be permanently attached to the injection device.Further, the injection device may be an injector pen.

An aspect of the disclosure provides a data collection device comprisinga first portion having one or more features configured for attaching ofthe first portion to a dosage knob of an injection device, a secondportion rotatably coupled with the first portion, wherein at least partof the second portion is movable axially relative to the first portion,a sensor arrangement configured to detect rotation of the first portionrelative to the second portion, and a processor arrangement configuredto, based on said detected movement, determine a medicament amountexpelled by the injection device, wherein the coupling arrangement isconfigured to provide a non-permanent coupling between the first portionand the dosage knob of the injection device.

The first portion may have an internal surface formed of a deformablematerial.

The first portion may have an internal surface shaped to correspond toexternal features of the dosage knob of the injection device.

The first portion may have an internal surface configured to mate withexternal features of the dosage knob of the injection device.

The internal surface of the first portion may include grooves thatcorrespond in shape with formations on the surface of the dosage knob ofthe injection device. The grooves may have mouths at an open end of thefirst portion and the grooves may taper to a narrower width away fromthe open end of the first portion.

The first portion may be provided with one or more external gripfeatures to facilitate gripping of the first portion by a user to effectrotation of the data collection device relative to a housing of theinjection device.

The user-accessible surface of the second portion may be larger than theuser-accessible portion of the first portion when the data collectiondevice is installed on the injection device.

The user-accessible surface of the first portion may be larger than theuser-accessible portion of the second portion when the data collectiondevice is installed on the injection device.

The second portion may be rotatably coupled with the first portion at alocation that is closer radially to a longitudinal axis of the datacollection device than it is to an outer diameter of the data collectiondevice.

In some examples, the second portion may be rotatably coupled with thefirst portion at a location that is radially further from thelongitudinal axis of the data collection device than it is to the outerdiameter of the data collection device, and optionally wherein thelocation is axially coincident with the location of the dosage knob whenthe data collection device is installed on the injection device.

The first portion may include an element configured to fit closelyaround a dose button of the injection device when the data collectiondevice is coupled to the injection device.

The data collection device may be configured to switch between a firstconfiguration in which rotation of the first portion relative to thesecond portion is prevented and a second configuration in which thefirst portion can be rotated relative to the second portion.

The sensor arrangement may comprise one or more of an optical sensor, amagnetic sensor, a capacitive sensor or a mechanical sensor.

The data collection device may further comprise an electrical switchconfigured to be operated upon movement of at least part of the secondportion relative to the first portion, wherein a force required tooperate the electrical switch is lower than a force required to causemedicament delivery from the injection device.

An aspect of the disclosure provides a medicament administrationapparatus which comprises an injection device comprising a rotatablecomponent configured to rotate as a medicament is expelled from theinjection device and a data collection device as set out above.

The injection device may comprise an injection button arranged to causeexpulsion of the medicament from the injection device; and the secondportion of the data collection device may be arranged to press on theinjection button when pressure is applied to the second portion.

In some embodiments, the injection device is a disposable injectiondevice and the data collection device is configured to be releasablyattachable to the injection device. In some embodiments, the injectiondevice may be a reusable injection device and the data collection devicemay be configured to be permanently attached to the injection device.Further, the injection device may be an injector pen.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting, exemplary embodiments of the disclosure will now bedescribed with reference to the accompanying drawings, of which:

FIG. 1 shows an exploded view of an example injection device for usewith a data collection device according to an embodiment of thedisclosure;

FIG. 2 depicts an example of a data collection device attached to theinjection device of FIG. 1 according to an exemplary embodiment;

FIG. 3 is a cross-sectional view of the data collection device shown inFIG. 2 when attached to the injection device of FIG. 1;

FIGS. 4a-4d are schematic drawings of example variations of a part ofthe data collection device of FIG. 2 that engages with the injectiondevice;

FIG. 5 depicts example locking formations on the data collection deviceof FIG. 2;

FIG. 6 is an isometric cutaway view of a first variation of the datacollection device of FIG. 2;

FIG. 7a is a proximal end isometric view of a second variation of thedata collection device of FIG. 2;

FIG. 7b is a distal end isometric view of the second variation of thedata collection device of FIG. 2;

FIG. 7c is a side view of the second variation of the data collectiondevice of FIG. 2;

FIG. 7d is a side cross-section view of the second variation of the datacollection device of FIG. 2;

FIG. 7e is a partial cutaway isometric proximal view of the secondvariation of the data collection device of FIG. 2;

FIG. 8 is a cross-sectional view of the second variation of the datacollection device of FIG. 2 installed on the injection device of FIG. 1;

FIG. 9a is a distal end isometric view of a third variation of the datacollection device of FIG. 2;

FIG. 9b is a proximal end isometric view of the third variation of thedata collection device of FIG. 2 installed on the injection device ofFIG. 1;

FIG. 9c is a side view of the third variation of the data collectiondevice of FIG. 2;

FIG. 9d is a cutaway side view of the third variation of the datacollection device of FIG. 2;

FIG. 9e is a side cross-section view of the third variation of the datacollection device of FIG. 2;

FIG. 10a is a distal end isometric view of a fourth variation of thedata collection device of FIG. 2;

FIG. 10b is a distal cutaway view of the fourth variation of the datacollection device of FIG. 2;

FIG. 10c is a side view of the fourth variation of the data collectiondevice of FIG. 2;

FIG. 10d is a side cross-section view of the fourth variation of thedata collection device of FIG. 2;

FIG. 11 is a block diagram of components of the data collection devicesof FIGS. 2 and 6-10;

FIG. 12 depicts an example system in which data from the data collectiondevice of FIGS. 2 and 6-10 is transmitted to another device;

FIG. 13 is a view of an example injection device for use with a datacollection device according to an embodiment of the disclosure; and

FIG. 14 is a block diagram of an example data collection deviceaccording to an embodiment of the disclosure, for use with the injectiondevice of FIG. 13.

DETAILED DESCRIPTION

The present specification discloses a data collection device which isattachable to a proximal end of an injection device, such as a peninjector, such as to fit the injector device like a cap. The datacollection device is configured such that it can be push-fitted over adosage knob or dose dialing knob of the injection device. In particular,a first portion of the data collection device includes a cavity thatreceives the dosage knob, and includes a deformable inner surface suchas to provide a tight fit over the dosage knob and/or has features thatmate closely with external features of the dosage knob. Through thepush-fit features, the data collection device can easily be installed onthe injection device, and can easily be removed through application of aremoval force between the data collection device and the injectiondevice in an axial direction. When installed, the data collection deviceis manipulated by the user in order to effect operation of the injectiondevice. The data collection device when installed monitors quantitiesand times of medicament delivery from the injection pen. Medicamentquantities can be transmitted, e.g. to a smartphone, and/or displayed ona display of the data collection device. By providing the datacollection device with push-fit features, it can be located onto andused with a series of different injection devices and thus monitor auser's medicament treatment over multiple devices. Moreover, this can beachieved without impeding normal use of the injection device and withoutobscuring a dosage window of the injection device.

In the following, embodiments of the present disclosure will bedescribed with reference to an insulin injection device. The presentdisclosure is however not limited to such applications and may equallywell be deployed with injection devices that eject other medicaments.

FIG. 1 is an exploded view of a medicament delivery device. In thisexample, the medicament delivery device is an injection device 1, suchas Sanofi's SoloSTAR® insulin injection pen.

The injection device 1 of FIG. 1 is a pre-filled, disposable injectionpen that comprises a housing 10 and contains an insulin container 14, towhich a needle 15 can be affixed. The needle is protected by an innerneedle cap 16 and either an outer needle cap 17 or an alternative cap18. An insulin dose to be ejected from injection device 1 can beprogrammed, or “dialed in” by turning a dosage knob 12, and a currentlyprogrammed dose is then displayed via dosage window 13, for instance inmultiples of units. For example, where the injection device 1 isconfigured to administer human insulin, the dosage may be displayed inInternational Units (IU), wherein one IU is the biological equivalent ofabout 45.5 micrograms of pure crystalline insulin (1/22 mg). Other unitsmay be employed in injection devices for delivering analogue insulin orother medicaments. It should be noted that the selected dose may equallywell be displayed differently than as shown in the dosage window 13 inFIG. 1.

The dosage window 13 may be in the form of an aperture in the housing10, which permits a user to view a limited portion of a number sleeve 70that is configured to move when the dosage knob 12 is turned, to providea visual indication of a currently programmed dose. The dosage knob 12is rotated on a helical path with respect to the housing 10 when turnedduring programming.

In this example, the dosage knob 12 includes one or more formations 71a, 71 b, 71 c to facilitate attachment of a data collection device to bedescribed hereinbelow.

The injection device 1 may be configured so that turning the dosage knob12 causes a mechanical click sound to provide acoustical feedback to auser. The number sleeve 70 mechanically interacts with a piston ininsulin container 14. When needle 15 is stuck into a skin portion of apatient, and then injection button 11 is pushed, the insulin dosedisplayed in display window 13 will be ejected from injection device 1.When the needle 15 of injection device 1 remains for a certain time inthe skin portion after the injection button 11 is pushed, a highpercentage of the dose is actually injected into the patient's body.Ejection of the insulin dose may also cause a mechanical click sound,which may be different from the sounds produced when using dosage knob12.

In this embodiment, during delivery of the insulin dose, the dosage knob12 is turned to its initial position in an axial movement (e.g., withoutrotation), while the number sleeve 70 is rotated to return to itsinitial position, e.g. to display a dose of zero units.

Injection device 1 may be used for several injection processes untileither the insulin container 14 is empty or the expiration date of themedicament in the injection device 1 (e.g. 28 days after the first use)is reached.

Furthermore, before using injection device 1 for the first time, it maybe necessary to perform a “prime shot” to remove air from insulincontainer 14 and needle 15, for instance by selecting two units ofinsulin and pressing injection button 11 while holding injection device1 with the needle 15 upwards. For simplicity of presentation, in thefollowing, it will be assumed that the ejected amounts substantiallycorrespond to the injected doses, so that, for instance the amount ofmedicament ejected from the injection device 1 is equal to the dosereceived by the user. Nevertheless, differences (e.g. losses) betweenthe ejected amounts and the injected doses may occur and may be takeninto account.

FIG. 2 is a perspective view of one end of the injection device 1 when adata collection device 20 according to an example embodiment isattached. The data collection device 20 includes a housing 21 and an endplate 22 with an optional display 22 a. The data collection device 20may take one of a number of different forms, as described below and asshown in the drawings.

FIG. 3 is a cross-sectional view of the data collection device 20according to an embodiment, when attached to the injection device 1. Thedata collection device 20 includes a first portion 23 and a secondportion 24, where the first portion 23 is capable of rotational movementrelative to the second portion 24.

In this particular example, the first portion 23 is a sleeve that ispositioned over the dosage knob 12. The first portion may haveformations 19 a, 19 b, 19 c that co-operate with the formations 71 a, 71b, 71 c on the dosage knob 12. Whether or not the formations 19 a-c areprovided on the first portion 23, the arrangement is such that, when thefirst portion 23 is rotated by a user during programming of the dosage,the dosage knob 12 also rotates and such that, when the dosage knob 12rotates during expulsion of medicament, the first portion 23 alsorotates.

Resilient padding, such as a foam rubber pad 44, may be provided withinthe formations 19 a-c on the first portion 23, to allow for tolerancesin the dimensions of the formations 19 a-c on the first portion 23 andthe formations 71 a, 71 b, 71 c on the dosage knob 12 and/or to providean engagement between the first portion 23 and the dosage knob 12 sothat rotation of the first portion 23 causes rotation of the dosage knob12 and vice versa. The resilient padding 44 may alternatively be made ofanother rubber or synthetic rubber material. The resilient padding 44may be provided around the entire circumference of the first portion 23,or it may be provided at intermittent locations.

As shown in FIG. 4 b, the resilient padding 44 may be providedalternatively to formations 19 a-c on the first portion 23. In someembodiments, the inner surface of the first portion 23 at the distal end35 (e.g., lowermost in FIG. 3) is substantially featureless. The innersurface may be generally cylindrical in shape. It may alternatively begenerally conical, being wider at the distal end. It may alternativelybe generally dome-shaped, being wider at the distal end.

Further, alternatively, the first portion 23 comprises a resilientpadding of sufficient thickness to render formations that co-operatewith the formations 71 a, 71 b, and 71 c on the dosage knob. The paddingis soft enough to conform to the surface of the dosage knob 12. Forexample, the padding is soft enough to conform to the formations on thesurface of the dosage knob 12.

In some embodiments (e.g., the embodiments of FIGS. 4 a, 4 c and 4 d),the resilient padding 44 may be provided in addition to formations onthe inner surface of the first portion 23.

The padding 44 described above can perform multiple functions. First, itassists in mounting the first portion 23 of the data collection device20 over the dosage knob 12. In particular, the resilient padding 44deforms to accommodate the dosage knob 12 within the cavity of the firstportion. Friction provides a reactive force in response to insertion ofthe dosage knob 12 within the first portion 23. This provides tactilefeedback to the user indicating that the data collection device 20 isbeing received over the dosage knob 12. Once the data collection device20 is installed fully, further movement is prevented. This can bedetected by the user through tactile feedback by providing the user witha step change from some relative movement to no relative movement as theproximal end of the dosage knob 12 abuts an abutting surface at theproximal end of the cavity in the first section 23 (see FIG. 6 forinstance). The friction between the data collection device 20 and thedosage knob 12 causes the data collection device 20 to remain installedon the injection device 1. This can be achieved without any furthermechanism to secure the data collection device 20 to the injectiondevice, although the use of a further mechanism is not precluded. Touninstall the data collection device 20 from the injection device, thefriction force needs to be overcome.

This can be achieved by applying a strong pulling force, for instance of30N or more, to the data collection device in the proximal direction.

The padding also provides sufficient engagement for transferringrotation force applied by the user between the first portion 23 and thedosage knob 12 during dose setting/programming.

The force is communicated by friction between the first portion 23 andthe dosage knob 12. The friction force acting between the first portion23 and the dosage knob 12 in the rotational direction exceeds the forcerequired to overcome the forces internal to the drug delivery device 1by a factor (e.g., of at least 5), or in some implementations, moreadvantageously at least a factor of 10, which helps to avoid slippagebetween the components.

As shown schematically in FIG. 4 a, the formations 19 a-c on the innersurface may take the form of features that have a shape that mates withthe shape of the formations 71 a, 71 b, 71 c on the dosage knob 12. Forinstance, the formations 19 a-c on the inner surface may take the formof features that have a shape corresponding closely to the shape of theformations 71 a, 71 b, 71 c on the dosage knob 12. Close correspondencein shape can allow good engagement between the first portion 23 and thedosage knob 12. Where the formations 19 a-c on the inner surface have ashape that mates with the shape of the formations 71 a, 71 b, 71 c onthe dosage knob 12, the choice of a material with a relatively highfriction coefficient to form the inner surface of the first portion 23contributes to providing a fit between the data collection device 20 andthe dosage knob 12 that results in retention of the data collectiondevice 20 on the injection device 1. The optional use of a resilientmaterial on the inner surface of the first portion 23 contributesfurther to retention of the data collection device 20 on the injectiondevice 1. However, if the fit between the formations on the innersurface of the first portion 23 and the formations 71 a, 71 b, 71 c onthe dosage knob 12 is sufficiently close and the coefficient of frictionbetween them is sufficiently high, the material of the inner surface ofthe first portion 23 need not be resilient.

As shown schematically in FIG. 4 c, the formations 19 a-c on theresilient inner surface of the first portion 23 may take the form ofribs. The ribs may have a triangular cross-section, or they may have adomed cross-section. The ribs may be circumferential. Alternatively,they may be axially arranged. Axial ribs advantageously number at leastfour times the number of formations 71 a, 71 b, 71 c on the dosage knob12. This can help to ensure that the formations 71 a, 71 b, 71 c on thedosage knob 12 can easily be received by the formations on the firstportion 23 without requiring specific rotational alignment.

As shown in FIG. 4 d, the formations 19 a, 19 b may take the form ofribs. When the data collection device 20 is placed over the dosage knob12, the formations 71 a-c of the dosage knob fall between theformations/ribs 19 a-c of the first portion 23. The formations 19 a, 19b here are configured such as to grip the surface of dosage knob 12between the formations 71 a-c when the data collection device 20 isinstalled fully onto the injection device 1. To this end, the ribs 19 a,19 b have a height in the radial direction that is equal to or greaterthan the radial height of the formations 71 on the dosage knob 12. Theribs are spaced and numbered such that it is unlikely that a proximalend of the ribs will contact a distal end of the formations on thedosage knob 12 when the data collection device is being installed. Inparticular, the spacing between adjacent ribs may be equal to an integermultiple of the spacing between adjacent formations 71 on the dosageknob 12. The configuration and spacing of the ribs may be such that ifthere is contact between a proximal end of a rib and a distal end of aformation on the dosage knob 12 when the data collection device is beinginstalled, there is substantially identical contact between multipleribs and multiple formations 71. When this happens, a small amount ofrotational force, which may be provided by the ribs glancing off theformations, causes the ribs to be located between the formations 71 onthe dosage knob 12.

The ribs may or may not be twisted with respect to the longitudinal axisof the data collection device 20. In particular, there may be a relativetwist between different formations 19 a-c, for instance oneformation/rib 19 a has a clockwise twist and the next formation/rib 19 bhas an counterclockwise twist. When the data collection device 20 isplaced over the dosage knob 12, the formations 71 a-c of the dosage knobfall between the formations/ribs 19 a-c of the first portion 23.

In various arrangements, the first portion 23 is shaped such that thereis substantially even engagement between the first portion 23 and thedosage knob 12 for the whole of the axial length of the dosage knob 12.This helps to ensure correct axial orientation of the data collectiondevice 20 with the injection device 1. Axial orientation is providedbecause the shapes of the components are such that any incorrectorientation results in a corrective force being applied radially betweenthe dosage knob 12 and the first portion 23 as they are mated together.Correct axial alignment is useful because it provides a bettertransmission of rotation force from the first portion 23 to the dosageknob 12 and because it provides better feedback to the user when dosedelivery is performed. It also generally improves the experience of theuser.

In some embodiments, the first portion 23 may be formed with a rigidsection surrounding at least part of the second portion 24 and aresilient section that surrounds at least part of the dosage knob 12,the rigid section providing a firm gripping surface for the user whenmounting or removing the data collection device 20 onto or from theinjection device 1 and the resilient section assisting in mounting thefirst portion 23 over the dosage knob 12 and providing sufficientengagement for transferring rotation between the first portion 23 anddosage knob 12 during programming and medicament expulsion. Optionally,the rigid section may be formed of a different material from theresilient section. Such a first portion 23 may, optionally, also includeformations 19 a-c configured to co-operate with the formations 71 a, 71b, 71 c on the dosage knob 12, as described above, and/or resilientpadding 44.

In some embodiments, an indicator is provided on the data collectiondevice. The indicator may for instance be a groove, a nose or a printedfeature. The indicator facilitates alignment by the user of the datacollection device with a nose of the injection device 1. However, insome embodiments (e.g., in the embodiments shown in the drawings), nosuch alignment is needed.

The coupling between the first portion 23 and the dosage knob 12 mayinclude no moving parts. The first portion 23 is coupled with the dosageknob 12 solely through a close fit, through friction between surfaces ofthe components, optionally assisted by deformation of a resilientmaterial forming the coupling surface of the first portion 23.

To set a medicament dosage amount to be administered, the user may gripand rotate the first portion 23, since this will cause the dosage knob12 of the injection device 1 to turn and, thereby, program the dosageamount.

Also, in this particular example, the second portion 24 is a bodylocated within the first portion 23, to which it is rotatably attachedusing bearings 25. The second portion 24 includes an outer portion 26,which includes the endplate 22 and optionally a display 22 a.

The second portion 24 also includes an inner portion 27. When the datacollection device 20 is attached to the injection device 1, the innerportion 27 overlies the injection button 11. The outer portion 26 andthe inner portion 27 are attached by a fixture 28 that prevents rotationrelative to each other. However, in this embodiment, the outer portion26 can be moved axially relative to the inner portion 27 and one or moreresilient members, such as springs 29, may be provided to bias the outerportion 26 away from the inner portion 27.

The data collection device 20 is configured to detect axial movement ofthe outer portion 26 relative to the inner portion 27. Movement greaterthan a predetermined amount may be detected using a switch 53, forinstance, as is described in more detail below.

In this particular arrangement, first electrical contacts 30 areprovided on the outer portion 26, while corresponding second electricalcontacts 31 are provided on the inner portion 27. When a user pressesthe endplate 22, the outer portion 26 moves axially towards the innerportion, establishing a connection between the first and secondelectrical contacts 30, 31. Further pressure on the endplate 22 causesthe inner portion 27 to press against, and activate, the injectionbutton 11. The first and second electrical contacts 30, 31 provide adata connection between the processor arrangement 50 and display 22 awhen engaged.

Optionally, the data collection device 20 may be arranged to have afirst configuration, in which rotation of the first portion 23 relativeto the second portion 24 is prevented, and a second configuration, inwhich such rotation is unimpeded. For example, as shown in FIG. 5, thefirst portion 23 and the second portion 24 may be provided with lockformations such as a protrusion 40 on one of the first and secondportions 23, 24 and a circumferential groove 41 and axial recess 42 onthe other of the first and second portions 23, 24. In this particularexample, in the first configuration, the protrusion 40 is located in therecess 42 and rotation is prevented. The data collection device 20 maybe switched to the second configuration by axial movement of the secondportion 24 relative to the first portion 23, so that the protrusion 40is located within the circumferential groove 41 and rotation ispermitted.

While the arrangement shown in FIG. 5 includes lock formations in theform of a protrusion 40, groove 41 and recess 42, other types ofco-operating formations or lock methods may be used to prevent rotationin the first configuration.

FIG. 6 is an isometric cutaway view of a first alternative datacollection device 240, which is a variation of the data collectiondevice 20.

FIGS. 7a to 7e are different views of a second alternative datacollection device 220, which is another variation of the data collectiondevice 20. FIG. 8 is a cross-sectional view of the second alternativedata collection device 220 installed on the injection device.

In these Figures, reference numerals are retained from FIG. 2 for likeelements. Unless otherwise stated or unless impossible, features of theFIG. 2 device are present in the

FIGS. 6-8 data collection devices. Also, features of any one device arepresent in all of the other devices.

The FIGS. 2, 5, 6, 7 and 8 data collection devices have a commoncharacteristic that the first portion 23 has a larger accessible surfacearea than does the second portion 24.

The data collection device 240 of FIG. 6 includes a capsule 244, whichis contained within the body of the data collection device 240. Thecapsule 244 itself contains a power source 54 or battery, in the form ofa coin cell in this example, and a printed circuit board (PCB) 242.Mounted on the PCB are a number of electronic components including acommunications interface 243, for instance a Bluetooth™ Low Energy chipor a Near Field Communications (NFC) chip. It also supports a switch 53for detecting axial movement of the second portion 24. The PCB 242further supports a sensor arrangement 51, which is configured to detectrotation of the first portion 23 relative to the second portion 24. Inparticular, the capsule 244 is fixed in rotation relative to the secondportion 24 and rotates with the second portion 24 relative to the firstportion 23 when the dose is being delivered.

The power source 54 provides power to the electronic components of thedata collection device 240. The power source 54 is located distally tothe PCB 242. The power source 54 is abutted by the distal end of thecapsule 244 and by the PCB 242.

The first portion 23 has three key structural elements. The firstportion 23 may be formed as one part, or it may be formed of multipleparts that are connected together. A first element 246 of the firstportion 23 is configured to engage with the dialing knob 12. Aspects ofthe first element are described above, especially in relation to FIGS.4a to 4 d. A second element 246 is configured to engage with the dosedelivery button 11. In particular, the second element 246 is configuredto fit closely around the dose delivery button 11. The second element246 helps to ensure correct axial alignment of the data collectiondevice 240 on the injection device 1. The second element 246 may takethe form of a ring. The second element 246 may have a low friction innersurface, so as not to impede movement of the dose delivery button 11 inthe distal direction. The third element 248 is located at the proximalend of the first portion 23. The third element 248 extends radiallyinwardly. It also surrounds the second portion 24 in the radialdirection.

The capsule 244 is movable in the axial direction within the cavityformed in the first portion 23. The capsule 244 is restrained in theproximal direction at the periphery of the capsule 244 by the thirdelement 248 of the first portion 23. In the distal direction, thecapsule 244 abuts the dose button 11.

The second portion 24 is connected at its periphery to a proximal end ofthe capsule 244. A pillar 245 is provided at the center of the secondportion 24 and extends axially. The pillar 245 is coincident with theswitch 53, and may or may not contact it when no force in the distaldirection is applied to the second portion 24. The center of the secondportion 24 is slightly deformable in the distal direction.

The switch 53 is configured to be operated upon movement of at leastpart of the second portion 24 relative to the first portion 23. A forcerequired to operate the switch 53 may be lower than a force required tocause medicament delivery from the injection device 1. By usingoperation of the switch 53 to trigger powering of components of the datacollection device, the components of the data collection device willthus be powered before dose delivery commences. For instance, the forcerequired to operate the switch 53 may be about 2 N, or more generallybetween 1 and 5 N.

Operation of the data collection device 240 will now be described.First, a user dials a dose into the injection device 1. This is achievedby the user rotating the first portion 23 of the data collection device240. The rotational force is communicated to the dosage knob 12, whichrotates also. The second portion 24 also rotates along with the firstportion when the dose is being dialed. During dialing, the electronicson the PCB 242 are not powered.

Once the user has dialed the desired dose, they press the second portion24 in order to start delivery of the dose, i.e. to cause injection.Initially, the second portion 24 deforms slightly and the center of thesecond portion 24 moves in the distal direction more than the peripheryof the second portion 24. In other words, the center of the secondportion 24 moves axially relative to the periphery of the second portionand axially relative to the first portion. This causes the pillar 245 toactivate the switch 53. This causes the electronics on the PCB 242 to bepowered and thus activated. Further movement of the second portion 24 iscommunicated into movement of the capsule 244 within the first portion23. This is communicated to movement of the dose button 11 in the distaldirection. Once the dose button 11 has moved enough to permit dosedelivery (which occurs by causing disengagement of a clutch, not shown,within the injection device 1), the dosage knob 12 begins to rotaterelative to the dose button 11 as the dose delivery button is moved inthe distal direction by action of the user. In particular, the dosedelivery button 11 does not rotate relative to the housing 10 of theinjection device 1, but the dosage button and the number sleeve 70 movehelically (i.e. they move axially and rotate simultaneously). The firstportion 23 thus rotates relative to the second portion 24. When the userceases to press on the second portion 24, or when all of the dose isdelivered, rotation of the first portion 23 relative to the secondportion 24 ceases. The amount of rotation that occurrs indicates thedelivered dose. The amount of rotation is detected by the sensor 51, andthis is used to calculate the delivered dose. The delivered dose is thenstored in memory, as described below.

The FIG. 6 data collection device is absent of a display, although adisplay for displaying a delivered dose may be provided.

Instead of the display, the FIG. 6 data collection device includes anoptical indicator arrangement. For instance, the optical indicatorarrangement may be one or two light sources, such as light emittingdiodes (not shown). The optical indicator arrangement may be providedaxially or peripherally on the proximal end face of the second portion24, or on the circumference of the second portion 24 or the firstportion 23, for instance.

The optical indicator arrangement is configured to provide feedbackregarding a dwell period. When the injection finishes, which is detectedby detecting the ceasing of rotation between the first and secondportions 23, 24 or the ceasing of operation of the switch 53, theoptical indicator arrangement of the data collection device indicatesthat a dwell time period is in place. For instance, the opticalindicator arrangement starts blinking, (e.g., the optical indicatorarrangement is activated intermittently). The frequency of blinking canchange over the dwell period. For instance, at the start of the dwellperiod the frequency may be about 5Hz and at the end of the period thefrequency may be about 1Hz. When the dwell period is finished, theoptical indicator arrangement may remain illuminated, to indicate theend of the sequence and the end of the dwell period.

The duration of the dwell period depends on the type of medicament. Thetype of medicament or the dwell time may be communicated to the datacollection device, for instance from a mobile phone running anapplication that is configured to operate in conjunction with the datacollection device.

The optical indicator arrangement is configured to provide feedbackregarding a medicament dose having already been taken recently. When theuser presses the second portion 24 of the data collection device, thedata collection device checks a time at which the last dose wasdelivered. The user may press the second portion 24 of the datacollection device in order to initiate delivery of medicament orspecifically to request information about the time since the last dosedelivery. The data collection device determines if the dose alreadytaken notification is to be provided by observation of the switch 53, acurrent time and a time of the last dose delivery. If it is determinedthat no significant dose (e.g. larger than 2 units) was delivered in acertain time period, for instance the previous hour, the opticalindicator arrangement indicates that delivery of medicament ispermitted. For instance, the optical indicator arrangement may glowgreen for one second. If instead it is determined that a significantdose was delivered within the certain time period, the optical indicatorarrangement may glow or flash an alert, for instance red in color.

The optical indicator arrangement is configured to provide feedbackregarding end of life of the data collection device. When an error oranother unsolvable issue such as an empty battery is detected, the datacollection device indicates this, for instance by operating the opticalindicator arrangement to blinking in red for at least several hours.

Once the user removes the distally directed force from the secondportion, spring force from within the injection device causes the dosebutton 11 to return the capsule 244 and the second portion 24 to theoriginal position.

The data collection device 220 of FIG. 7 is very similar to the datacollection device of FIG. 6. However, a different mechanism retains thesecond portion 24 in the distal direction. The injection device 1 isabsent from FIGS. 7a to 7 e, but is shown in FIG. 8.

In FIGS. 7b and 7 d, the formations 19 a-c are shown clearly. It will beseen that the formations have two main parts. A proximally located part221 is a recess having a shape that corresponds well with the shape ofthe corresponding formation 17 on the dosage knob 12 in every dimension.A distally located part 222 has a mouth that flares outwardly in thedistal direction. The mouth of the part 222 serves to catch the proximalend of a formation 17 of the dosage knob 12 as the data collectiondevice 240 is placed onto the injection device 1. The sides of the mouththen cause adjustment of the rotational alignment so that the formations17 on the dosage knob 12 are guided into the proximally located part 221of the formations 19 a-c of the first portion 23. When fully installed,the distally located part 222 of the formations 19 a-c on the firstportion 23 are engaged in the radial direction with the formations 17 onthe dosage knob 12. This helps to keep correct axial alignment of thedata collection device 220 on the injection device 1 and helps to retainthe data collection device 220 on the injection device through friction.

Although described particularly with reference to FIGS. 7a and 7 d, theconfiguration and operation of the formations 19 may be the same on allof the data collection devices embodied in this specification.

The second portion 24 includes the pillar 245. The third element 248 ofthe first portion 23 includes a radially inwardly extending collar 225.The capsule 244 includes an annular neck portion 224. The neck portion224 fits around the pillar 245 in a rotationally locked connection. Thepillar 245 can move in the distal direction relative to the capsule 244by a small amount, to activate the switch 53 as the dose deliveryprocedure is commenced, but before dose delivery starts, but otherwiseis not movable relative to the capsule 244.

The pillar 245 and the neck portion 224 have interoperating featuresthat limit axial movement of the components relative to each other. Inparticular, one or more protrusions 228 fit into one or more indents229. The movement of the second portion 24 relative to the capsule 244is limited by the ends of the one or more indents 229 as regards the oneor more protrusions 228. In this example, the protrusions 228 areprovided on the pillar 245 and the indents 229 are provided on the neckportion 224, but alternative arrangements will be envisaged by a personskilled in the art.

A low friction surface is provided between the radially inward end ofthe collar 225 and the radially outward surface of the neck 224. Thus,the first portion 23 and the capsule 244 are able to rotate relative toone another during dose delivery. The second portion 24 is rotatablycoupled with the first portion at a location that is closer radially tothe longitudinal axis of the data collection device 240 than it is tothe outer diameter of the data collection device. The provision of thecontact surfaces of the first portion 23 and the capsule 244/secondportion 24 at a relatively radially inward positon is advantageous. Inparticular, it reduces the area of contact, which thus reduces friction.Thus, less torque is required to rotate the first portion 23 and thesecond portion 24 relative to one another during dose delivery. Thisimproves drug delivery and makes the combination of the injection device1 and the data collection device 220 easier to use.

A slotted disc 249, visible in FIG. 7 e, allows the sensor 51 to detectthe amount of rotation of the first portion 23 relative to the secondportion 24. In particular, a photodiode or other optical sensor 51 onone portion, for instance the second portion 24, is directed at theslotted disc 249, which rotates with the other portion, for instance thefirst portion 23. The sensor 51 detects light which is reflected ortransmitted by an amount that varies according to the position of theslots relative to the sensor 51 as the slotted disc 249 moves. Rotationof the slotted disc 249 relative to the sensor 51 thus causes the signaldetected by the sensor to change.

There are two main alternatives for using the sensor output to determinethe amount of rotation. First, the number of high intensity or lowintensity pulses can be counted, to derive the amount of rotation. Highor low intensity pulses can be detected for instance using a thresholdcircuit. Alternatively, the number of changes from low intensity to highintensity, or vice versa, can be counted. Changes can be determinedusing a differentiator circuit, for instance. Counting the number ofchanges provides good reliability because it does not depend on acorrect intensity threshold being used. In either case, the number ofslots passing the sensor 51 is counted, and therefrom the dose deliveredcan be calculated.

The FIGS. 7 and 8 data collection device is absent of a display,although a display for displaying a delivered dose may instead beprovided.

Operation of the data collection device 220 of FIGS. 7 and 8 will now bedescribed. First, a user dials a dose into the injection device 1. Thisis achieved by the user rotating the first portion 23 of the datacollection device 220. The rotational force is communicated to thedosage knob 12, which rotates also. The second portion 24 also rotatesalong with the first portion when the dose is being dialed. Duringdialing, the electronics on the PCB 242 are not powered.

Once the user has dialed the desired dose, they press the second portion24 in order to start delivery of the dose, i.e. to commence injection.Initially, the second portion 24 moves in the distal direction from oneend to the other end of the distance permitted by interoperation of theone or more protrusions 228 fit into one or more indents 229. At orclose to the limit of travel, the location of the second portion 24activates the switch 53. This causes the electronics on the PCB 242 tobe powered and thus activated. Further movement of the second portion 24is communicated into movement of the capsule 244 within the firstportion 23. This is communicated to movement of the dose button 11 inthe distal direction. Once the dose button 11 has moved enough tocommence dose delivery, the dosage knob 12 begins to rotate relative tothe rest of the injection device 1, including the dose button 11. Thefirst portion 23 thus rotates relative to the second portion 24. Whenthe user ceases to press on the second portion 24, or when all of thedose is delivered, rotation of the first portion 23 relative to thesecond portion 24 ceases. The amount of rotation that occurred indicatesthe delivered dose. The amount of rotation is detected by the sensor 51,and this is used to calculate the delivered dose. The delivered dose maythen be displayed on the display 22 a and/or stored in non-transientmemory or transient memory, which may or may not be part of theprocessor arrangement.

Once the user removes the distally directed force from the secondportion, spring force from within the injection device causes the dosebutton 11 to return the capsule 244 and the second portion 24 to theoriginal position.

FIGS. 9a to 9e are different views of a third alternative datacollection device 120, which is a variation of the data collectiondevice 20.

FIGS. 10a to 10d are different views of a fourth alternative datacollection device 140, which is a variation of the data collectiondevice 20.

In these Figures, reference numerals are retained from FIGS. 2, 6, 7 and8 for like elements. Unless otherwise stated or unless impossible,features of the FIGS. 2, 6, 7 and 8 data collection devices are presentin the FIGS. 9 and 10 data collection devices. Also, features of any onedevice are present in all of the other devices unless otherwise stated.

The FIGS. 9 and 10 data collection devices have a common characteristicthat the second portion 24 has a larger user-contactable externalsurface area than does the first portion 23.

The shape of the second element 247 of the first portion 23, whichserves to guide the data collection device to correct axial alignmentusing the dose button 11, is clearly visible in FIGS. 9a and 9 e. Thedose button 11 is shown in a depressed state in FIG. 9 a, so it is notshown engaging the second element 247 of the first portion 23 in thisFigure. Second element 247 is shaped such that it at least partly fitsaround a dose button of the injection device when the data collectiondevice is coupled to the injection device.

In the FIG. 9 data collection device 120, the second portion 24 isrelatively large. Within the second portion 24, a spring 121 biases twopower source (e.g. batteries) 54 against the distal face of the PCB 242.A conductor 122 forms an electrical circuit between the proximal face ofthe proximal power source 54 and the PCB 242. The switch 53 is formed onthe proximal face of the PCB 242. The switch 53 may include a springterminal, as shown in the Figure. The spring terminal is moved, therebyto operate the switch 53, upon movement of the second portion 24 in thedistal direction relative to the first portion 23. A force required tooperate the switch 53 is lower than the force required to causemedicament delivery from the injection device 1. By using operation ofthe switch 53 to trigger powering of components of the data collectiondevice, the components of the data collection device will thus bepowered before dose delivery commences. For instance, the force requiredto operate the switch 53 may be about 2 N, or more generally between 1and 5 N.

A first collar 124 is directed in a distal direction from the distal endof the capsule 244. A second collar 125 extends distally from the distalend of the capsule 244. The second collar 125 is outside of the firstcollar 124, and they are concentric.

The second collar 125 and the second portion 24 have interoperatingfeatures that limit axial movement of the components relative to eachother. In particular, one or more protrusions 228 fit into one or moreindents 229. The movement of the second portion 24 relative to thecapsule 244 is limited by the ends of the one or more indents 229 asregards the one or more protrusions 228. In this example, theprotrusions 228 are provided on the second collar 125, and thus thecapsule 244, and the indents 229 are provided on the second portion 24,but alternative arrangements will be envisaged by a person skilled inthe art.

The first collar 124 snugly fits the dose button 11, to assist in axialalignment between the data collection device 120 and the injectiondevice 1 during delivery. A washer (not shown) may be provided betweenthe first collar 124 and the dose button 11, to improve contact betweenthe components. The first collar 124 does not contact the first portion23 during installation of the data collection device 120 nor during dosedelivery.

The first portion 23 is provided with grip features 123. These allow auser to grip the first portion so as to provide torque and thus rotatethe first portion when setting a dose. The grip features 123 providesurfaces that extend generally radially, to which the user can provideforce to cause rotation of the first portion 23.

As can be seen best from FIG. 9 e, the first portion 23 is coupled tothe second portion 24 by a connector arrangement 230, 231, 228. Inparticular, the first portion 23 includes a first L section component231, which has an abutting surface facing in the distal direction. Thisis formed as part of the first portion 23. A second L section component230, forming part of the second portion 24, is coupled to a support 232,which is coupled to the PCB 242, the first collar 124 and othercomponents of the second portion 24. The second L section component 230has an abutting surface facing in the proximal direction. The second Lsection component 230, and the other components that are coupled to it,are attached to the first section 23 during manufacture by applicationof a force to cause a snap fit such that the abutting surfaces of thefirst and second L section components 231, 230 are located together.

The snap fitting of the second L section component 230 over the first Lsection component 231 is facilitated by a sloping face of the first Lsection component 231, which faces slightly in the proximal direction.

After the power source 54 has been included within the second section24, the main body 234 of the second portion, with the third L sectioncomponent 228 already fitted, is snap fitted over the second L sectioncomponent 230. The snap fitting is facilitated by a sloping face of thethird L section component 228, which faces slightly in the distaldirection. A proximally facing abutting surface of the third L sectioncomponent then abuts a distally facing abutting surface of the second Lsection component 228. This arrangement keeps the spring 121 incompression, thereby ensuring good electrical connection of the powersource 54. It also allows for a simple manufacturing process and the useof low cost components.

Once the first portion 23 is fitted to the second portion 24, the twoportions rotate relative to one another by a low friction contactbetween surfaces of the first and second L section components 230, 231.The low friction contact may be provided by suitable coating of therelevant surfaces, or by suitable material choice of the componentsthemselves.

During installation of the data collection device 120 on the injectiondevice 1, force is applied in an axial direction. During installation,the user is likely to apply force to the second portion 24. In thiscase, the force is communicated to the first portion, to result infitting of the first portion 23 over the dosage knob 12, by the distalend of the third L section component 228, or more generally the mainbody 234, against a proximally facing surface 235 of the first portion23. A spring force provided by the data collection device 120 forces thesecond portion 24 in the proximal direction relative to the firstportion 23, after installation. This spring force is greater than areaction force that is provided by the injection device 1 during dosedelivery (the reaction force results primarily from friction frommovement of internal components and hydrodynamic force resulting frommedicament expulsion through the needle). Thus, the distal end of thethird L section component 228, or more generally the main body 234, doesnot contact the proximally facing surface 235 of the first portion 23during dose delivery. If they were to be in contact during dosedelivery, a friction force would oppose rotational movement between thefirst portion 23 and the second portion 24.

The FIG. 9 data collection device 220 is absent of a display, although adisplay for displaying a delivered dose may instead be provided.

Operation of the data collection device 220 of FIG. 9 will now bedescribed. First, a user dials a dose into the injection device 1. Thisis achieved by the user rotating the first portion 23 of the datacollection device 220. The rotational force is communicated to thedosage knob 12, which rotates also. The second portion 24 also rotatesalong with the first portion when the dose is being dialed. Duringdialing, the electronics on the PCB 242 are not powered.

Once the user has dialed the desired dose, they press the second portion24 in order to start delivery of the dose, i.e. to cause injection.Initially, the second portion 24 moves in the distal direction from oneend to the other end of the distance permitted by interoperation of theone or more protrusions 228 and the one or more indents 229. At or closeto the limit of travel, the location of the second portion 24 activatesthe switch 53. This causes the electronics on the PCB 242 to be poweredand thus activated. Further movement of the second portion 24 iscommunicated into movement of the capsule 244 in the distal direction.This is communicated to movement of the dose button 11 in the distaldirection. Once the dose button 11 has moved enough to commence dosedelivery, the dosage knob 12 begins to rotate relative to the rest ofthe injection device 1, including the dose button 11. The first portion23 thus rotates relative to the second portion 24. When the user ceasesto press on the second portion 24, or when all of the dose is delivered,rotation of the first portion 23 relative to the second portion 24ceases. The amount of rotation that occurred indicates the delivereddose. The amount of rotation is detected by the sensor 51, and this isused to calculate the delivered dose. The delivered dose may then bedisplayed on the display 22 a.

Once the user removes the distally directed force from the secondportion, spring force from within the injection device causes the dosebutton 11 to return the capsule 244 and the second portion 24 to theoriginal position.

Because the first portion 23 is relatively small and because no part ofthe first portion is near to the proximal face of the second portion 24,the user is easily able to avoid contacting the first portion 23 whenusing the second portion 24 to cause dose delivery. This is the sameregardless of whether the user uses their thumb or their index finger tomanipulate the second portion 24.

The FIG. 10 data collection device 140 is very similar to the FIG. 9data collection device 120.

One main difference is that the data collection device 141 includes agrip element 141 formed of a high friction material, instead of macrofeatures 123, to provide a grip by which the user can dial a dose intothe injection device. The grip element 141 is in the form of a band. Thegrip element is fitted into a groove 142 that is provided on the outsidesurface of the first portion 23.

Another main difference is that the data collection device 140 isgenerally conical shaped. The diameter of the data collection device 140is greater at the proximal end than it is at the distal end. Thisfurther facilitates the user being able to avoid contacting the firstportion 23 when using the second portion 24 to cause dose delivery. Thisis the same regardless of whether the user uses their thumb or theirindex finger to manipulate the second portion 24.

FIG. 10b shows the slotted disc 249 that allows rotation of the firstportion 23 relative to the second portion 24 to be detected andmeasured. The slotted disc 249 is of the corrugated type in thisexample. Here, the slots do not extend all the way through the disc 249but form pits or grooves. The bottoms of the pits or grooves may bedifferently reflective to the surface of the disc that is closest to thesensor. Thus, movement of the disc 249 can be detected in substantiallythe same was as described above with reference to FIG. 7 e. Furtheralternatively, instead of having a slotted disc, the surface of firstportion 23 that is opposite to sensor 51 may be designed to bedifferently reflective in an alternating pattern.

The FIG. 10 data collection device is absent of a display, although adisplay for displaying a delivered dose may instead be provided.

FIG. 11 is a block diagram of the data collection device 20, 120, 140,220, 240. The data collection device 20 includes a processor arrangement50 including one or more processors, such as a microprocessor, a DigitalSignal Processor (DSP), Application Specific Integrated Circuit (ASIC),Field Programmable Gate Array (FPGA) or the like, together with memoryunits 52 a, 52 b, including program memory 52 a and main memory 52 b,which can store software for execution by the processor arrangement 50and data generated during use of the data collection device such ascounted pulses, derived dose size, time stamp, etc. The switch 53connects the power source 54 to the electronic components of the device,including the sensor arrangement 51, when operated. The display 22 a mayor may not be present.

The first and second electrical contacts 30, 31 may provide a dataconnection between the processor arrangement 50 and display 22 a whenengaged.

A sensor arrangement 51, comprising one or more sensors, is provided fordetecting rotational movement between the first portion 23 and thesecond portion 24.

The resolution of the sensing arrangement 51 is determined by the designof the injection device 1. A suitable angular resolution of the sensingarrangement 51 may be determined by Equation (1):

$\begin{matrix}{{resolution}{= \frac{360^{o}}{{units\_ per}{\_ rotation}}}} & (1)\end{matrix}$

For instance, if one full rotation of the dosage knob 12 corresponds toa medicament dosage amount of 24 IU, then a suitable resolution for thesensing arrangement 51 would be not more than 15°.

In the FIG. 2 embodiment, one or more first magnets 56 a are providedaround a circumference of the inner surface of the first portion 23 andone or more second magnets 56 b are provided around a circumference ofthe outer surface of the second portion 24, as shown in FIGS. 3 and 11.The sensor arrangement 51 is a transducer that varies its output due tovariations in the magnetic field, based on the Hall effect, as the firstportion 23 and first magnets 56 a rotate relative to the second portion24 and second magnets 56 b.

Since the first portion 23 rotates with the dosage knob 12 as medicamentis expelled from the injection device 1, the angle of rotation measuredby the sensing arrangement 51 is proportional to the amount ofmedicament expelled. It is not necessary to determine a zero level or anabsolute amount of medicament contained in the injection device 1.Moreover, since it is not necessary to monitor the numbers or tick markson the number sleeve 70 displayed through the dosage window 13, the datacollection device 20 may be designed so that it does not obscure thedosage window 13.

The medicament amount delivered is determined by the data collectiondevice 20 independent from the dosage that is programmed into theinjection device 1. Determining the delivered medicament amount providesa direct and thus more reliable information about the amount ofmedicament that is injected compared to data collection devices thatdetermine the amount of medicament that is set, thus being intended tobe dispensed.

However, in other embodiments, different types of sensor may be used.For example, instead of a transducer, the sensor arrangement may includea microelectromechanical (MEMS) device or other magnetic sensor fordetecting changes in a magnetic field. Another example of an sensingarrangement is an optical encoder, including a light source, such as alight emitting diode (LED) and a light detector, such as an opticaltransducer, that monitors changes in light reflected from an innersurface of the first portion, where the inner surface first portion hasone or regions of varying reflectivity around its circumference, such astick marks or at least one shaped reflective region. Such a sensorarrangement is used in the second to fourth variations described above.

In some embodiments, the sensing arrangement 51 may be a potentiometer.In yet another embodiment, a capacitive sensing arrangement may be used,where elements provided on the first portion 23 affect the capacitancebetween two plates in the sensing arrangement. In further examples,mechanical sensors, with mechanical switches and/or tracks, may be usedto detect the relative rotation between the first and second portions23, 25.

While the embodiments described in detail includes only certain types ofsensor in the sensor arrangement 51, other embodiments may be devised inwhich the sensor arrangement 26 includes multiple sensors of one or moretypes.

An output 57 is provided, which may be a wireless communicationsinterface for communicating with another device via a wireless networksuch as Wi-Fi or Bluetooth™, or an interface for a wired communicationslink, such as a socket for receiving a Universal Series Bus (USB),mini-USB or micro-USB connector. FIG. 12 depicts an example of a systemin which the data collection device 20 is connected to another device,such as a personal computer 60, via a wired connection 61 for datatransfer. For example, the processor arrangement 50 may store determineddelivered medicament amounts and time stamps for the injections as theyare administered by the user and subsequently, transfer that stored datato the computer 60. The computer 60 maintains a treatment log and/orforwards treatment history information to a remote location, forinstance, for review by a medical professional.

According to this embodiment, the data collection device 20 isconfigured to store data such as delivered medicament amounts and timestamps of up to 35 injection events, According to a once-daily injectiontherapy this would be sufficient to store a treatment history of aboutone month. Data storage is organized in a first-in first-out mannerensuring that most recent injection events are always present in thememory of the data collection device 20. Once transferred to a computer60 the injection event history in the data collection device 20 will bedeleted. Alternatively, the data remains in the data collection device20 and the oldest data is deleted automatically once new data is stored.In this way, the log in the data collection device is built up over timeduring usage and will always comprise the most recent injection events.Alternatively, other configuration could comprise a storage capacity of70 (twice daily), 100 (three months) or any other suitable number ofinjection events depending on the therapy requirements and/or thepreferences of the user.

In some embodiments, the output 57 may be configured to transmitinformation using a wireless communications link and/or the processorarrangement 23 may be configured to transmit such information to thecomputer 40 periodically.

A power switch 58 is provided, together with a power source 59. In someembodiments, the power switch 58 may be provided by the first and secondelectrical contacts 30, 31, or the switch 53 where the power switch 58responds to pressure applied to the second portion 24 by powering thedata collection device 20 on or off, so that power may conserved whenthe injection device 1 is not being used. In such an arrangement, thedata collection device 20 is powered on again, the processor arrangement50 may control the display 22 a to show the determined medicament doseinformation 22 a, to aid the memory of the user, and/or an elapsed timesince the determined medicament dose was delivered. For example, theprocessor arrangement 23 may cause the display 22 to switch periodicallybetween displaying the most recent determined medicament dosageinformation and the elapsed time.

The power source 54 may be a battery. In some embodiments, the endplate22 may include a solar panel to recharge a rechargeable battery. Thepower source may be a coin cell, or multiple coin cells arranged inseries or parallel.

In another embodiment, the power source 54 may be a piezo-electricgenerator, which generates power when the endplate 22 is pressed by theuser, potentially avoiding the need for a battery.

A timer 55 is also provided. In addition to, or instead of, switchingthe data collection device 20 on and off, the switch 53 or the first andsecond electrical contacts 30, 31 may be arranged to trigger the timer55 when engaged and/or disengaged. For example, if the timer 55 istriggered on both engagement or disengagement of the first and secondelectrical contacts 30, 31, or both operation and ceasing of operationof the switch 53, then the processor arrangement 50 may use the outputfrom the timer to determine a length of time during which the injectionbutton 11 was pressed, for example to determine the duration of aninjection.

Alternatively, or additionally, the processor arrangement 50 may use thetimer 55 to monitor a length of time that has elapsed since an injectionwas completed, as indicated by a time of disengagement of the first andsecond electrical contacts 30, 31 or ceasing of operation of the switch53. Optionally, the elapsed time may be shown on the display 22 a, asdepicted in FIG. 2. Also optionally, when the first and second contacts30, 31 are next engaged or when the switch 53 is next operated, theprocessor arrangement 50 may compare the elapsed time with apredetermined threshold, to determine whether a user may be attemptingto administer another injection too soon after a previous injection and,if so, generate an alert such as an audible signal and/or a warningmessage on the display 22 a. On the other hand, if the elapsed time isvery short, it may indicate that the user is administering a medicamentamount as a “split dose”, and the processor arrangement 50 may storeinformation indicating that a dosage was delivered in that manner. Insuch a scenario the elapsed time is compared with a predeterminedthreshold in the range of a few seconds, e.g. 10 seconds up to a fewminutes, e.g. 5 minutes. According to an example the predeterminedthreshold is set to 2 minutes. If the time elapsed since the lastinjection is two minutes or less, the processor arrangement 50 storesinformation indicating that the dosage was delivered as a “split dose”.Another optional purpose for monitoring the elapsed time by theprocessor arrangement 50 is to determine when the elapsed time haspassed a predetermined threshold, suggesting that the user might haveforgotten to administer another injection and, if so, generate an alert.

The data collection device 20 is used where the injection device 1includes a component that can rotate as medicament is dispensed.However, in some injection devices, the dosage knob does not rotateduring dose delivery. However, there may be another rotatable componentclose to the dose knob to which the first portion 23 can be attacheddirectly or indirectly. FIG. 13 depicts an example of such an injectiondevice 80. In FIG. 13, components similar to those of the injectiondevice 1 shown in FIG. 1 are indicated using the same reference labels.Also, the injection device 80 is shown with its cap 18 in place,covering the needle and medicament chamber.

In this particular example of an injection device 80, the injectionbutton and dosage knob are provided by a single component, knob 81. Amedicament dosage can be programmed into the injection device 72 byturning the knob 81, which rotates a sleeve 82 which extends outwardsfrom a housing 83 of the injection device 70 as the programmed dosageincreases.

As described above in relation to FIG. 1, turning the knob 81 also turnsa number sleeve 70, so that a dosage amount is displayed in the dosagewindow 13.

When the knob 81 is pressed to administer an injection or prime shot,the knob 81 is partially decoupled from the sleeve 82, so they canrotate independently of one another. As medicament is expelled from theinjection device 80, the sleeve 82 rotates and moves into the housing83. Meanwhile, the knob 81 moves towards the housing but does notrotate.

FIG. 14 is a block diagram of a data collection device 72 according to afurther embodiment, which is capable of being used with the injectiondevice 80 of FIG. 13 that does not have a rotatable component to whichthe first portion can be directly attached. Components of the datacollection device 72 that correspond to those of the data collectiondevice 20 of FIG. 2 are shown with the same reference labels.

The data collection device 72 is provided with a transfer arrangement73. The transfer arrangement 73 is configured so that, when the datacollection device 72 is attached to the injection device, it engages acomponent of the injection device that rotates as medicament isexpelled. The transfer arrangement 73 responds to rotation of therotatable component by causing the first portion 74 to rotate relativeto the second portion 75.

In this particular example, the transfer arrangement 73 is mounted onthe second portion 75 includes a friction wheel 76. In this particularexample, the friction wheel 76 has a substantially spherical, or ball,shape, so that the friction wheel 76 can pass over the knob 81 when thedata collection device 72 is mounted to the injection device 80 and toallow for axial movement between the first portion 74 and second portion75, for example when using a locking mechanism similar to that describedwith reference to the data collection device 20 and FIG. 5. The frictionwheel 76 may be attached to the second portion 75 by a resilient arm 77,to facilitate movement of the friction wheel 76 over the knob 81 whenmounting or removing the data collection device 72.

While FIG. 14 depicts an embodiment in which the transfer arrangement 73includes one friction wheel 76, other embodiments may include one ormore additional friction wheels 76, such as two or three frictionwheels. The provision of such additional friction wheels 76 may improvethe reliability of transfer of rotation between the sleeve 82 and firstportion 74.

As shown in FIG. 14, the knob 81 of the injection device 80 is incontact with the second portion 75. One or more resilient pads 45 may beprovided between the second portion 75 and knob 81 to improve engagementtherebetween. One or more of formations, not shown, configured toco-operate with formations 71 a, 71 b, 71 c on the knob 81 of theinjection device 80, resilient pads 84 and resilient portions in thesecond portion 75 may be provided to enhance engagement between thesecond portion 75 and the knob 81, so that rotation of the secondportion 75 causes rotation of the knob 81 and vice versa.

However, there first portion 74 does not contact, or engage directlywith, the knob 81. Therefore, the first portion 74 and second portion 75may be locked together, as described above in relation to FIG. 5, sothat the injection device 80 can be programmed by turning the firstportion 74, to rotate the second portion 75 and, therefore, the knob 81.When the dosage amount has been programmed, the user may press thesecond portion 75, which in turn depresses the knob 81, to dispense theprogrammed amount of medicament from the injection device 80. The axialmovement of the second portion 75 relative to the first portion 74,releases the locking mechanism that prevents rotation of the firstportion 74 relative to the second portion 75.

As the medicament is expelled, the knob 81 moves towards the housing 83but does not rotate. The sleeve 82 rotates while it moves back into thehousing 83. The rotation of the sleeve 82 is transferred to the firstportion 74 through the transfer arrangement 73. Therefore, the firstportion 74 is caused to rotate relative to the second portion 75. Thesensor arrangement 51 then detects the angle of rotation from which themedicament dosage amount can be determined, as described above inrelation to the data collection device 20 of FIG. 2.

The specific embodiments described in detail above are intended merelyas examples of how the present disclosure may be implemented. Manyvariations in the configuration of the data collection device 20, 120,140, 240, 220 and/or the injection device 1, 80 may be used. Some suchvariations will now be described.

The switch 53 in the FIG. 2 embodiment is formed of electrical contacts,and in the first to fourth variations of a switch. The switch may forinstance be a lever switch, a dome switch, a slider switch, a rubberkeypad switch. It may be a capacitive touch switch or a resistive touchswitch. It may be a tactile micro switch. The switch 53 may be generallyreferred to as a microswitch.

The first portion 23 may facilitate gripping by the user through radialfeatures, as shown in FIG. 9, or a rubberized component, as shown inFIGS. 10. Alternatively, the peripheral surface of the first portion 23may be roughened, or provided with an adhesive or tactile coating, bemade of or coated with a high friction material, or have some othergripable features.

In some embodiments, a spring element is coupled to a center of thedistal end of the capsule 242 at a center, proximal portion and iscoupled to the first portion 23 at a distal, peripheral portion. Afeature, for instance a depression, is provided on the capsule 244 toreceive the center part of the spring element. When the second portion24 is not being pressed in the distal direction, the spring element maynot contact the dose button 11. When the second portion 24 is beingpressed in the distal direction, the spring element compresses andcommunicates the force to the dose button 11. This arrangement canprovide a low-friction rotation center for rotation of the first portion23 relative to the second portion 24, along with guidance for thelocation of the capsule 244. It can also provide good axial tolerancecompensation. Furthermore, by choosing a spring that does not compresssignificantly upon application of a force that is sufficient to operatethe switch 53, this can provide good serial activation of the switchprior to activation of the dose delivery mechanism of the injectiondevice 1.

Also, while the embodiments above have been described in relation tocollecting data from an insulin injector pen, it is noted thatembodiments of the disclosure may be used for other purposes, such asmonitoring of injections of other medicaments.

The injection device 1 is configured to inject or infuse a medicamentinto a patient. For example, delivery could be sub-cutaneous,intra-muscular, or intravenous. Delivery could be needleless. Theinjection device 1 could be operated by a patient or caregiver, such asa nurse or physician, and may be one of various types of safety syringe,pen-injector, or auto-injector. The injection device 1 can include acartridge-based system that requires piercing a sealed ampule beforeuse. Volumes of medicament delivered with these various devices canrange from about 0.5 ml to about 2 ml. The injection device 1 may be alarge volume device (“LVD”) or patch pump, configured to adhere to apatient's skin for a period of time (e.g., about 5, 15, 30, 60, or 120minutes) to deliver a “large” volume of medicament (typically about 2 mlto about 10 ml). In combination with a specific medicament, theinjection device 1 may also be customized in order to operate withinrequired specifications. For example, the injection device 1 may becustomized to inject a medicament within a certain time period (e.g.,about 3 to about 20 seconds for auto-injectors, and about 10 minutes toabout 60 minutes for an LVD). Other specifications can include a low orminimal level of discomfort, or to certain conditions related to humanfactors, shelf-life, expiry, biocompatibility, environmentalconsiderations, etc. Such variations can arise due to various factors,such as, for example, a drug ranging in viscosity from about 3 cP toabout 50 cP. Consequently, the injection device 1 may include a hollowneedle ranging from about 25 to about 31 Gauge in size. Common sizes are27 and 29 Gauge.

The injection device 1 can also include one or more automated functions.For example, one or more of needle insertion, medicament injection, andneedle retraction can be automated. Energy for one or more automationsteps can be provided by one or more energy sources. Energy sources caninclude, for example, mechanical, pneumatic, chemical, or electricalenergy. For example, mechanical energy sources can include springs,levers, elastomers, or other mechanical mechanisms to store or releaseenergy. One or more energy sources can be combined into a single device.Devices can further include gears, valves, or other mechanisms toconvert energy into movement of one or more components of a device.

The one or more automated functions of such an injection device 1 mayeach be activated via an activation mechanism. Such an activationmechanism can include one or more of a button, a lever, a needle sleeve,or other activation component. Activation of an automated function maybe a one-step or multi-step process. That is, a user may need toactivate one or more activation components in order to cause theautomated function. For example, in a one-step process, a user maydepress a needle sleeve against their body in order to allow injectionof a medicament to be provided. The injection device 1 may require amulti-step activation of an automated function. For example, a user maybe required to depress a button and retract a needle shield in order tocause injection.

In addition, activation of one automated function may activate one ormore subsequent automated functions, thereby forming an activationsequence. For example, activation of a first automated function mayactivate at least two of needle insertion, medicament injection, andneedle retraction. The injection device 1 may also require a specificsequence of steps to cause the one or more automated functions to occur.The injection device 1 may operate with a sequence of independent steps.

The injection device 1 can include one or more functions of a safetysyringe, pen-injector, or auto-injector. For example, the injectiondevice 1 may include a mechanical energy source configured toautomatically inject a medicament (as typically found in anauto-injector) and a dose setting mechanism (as typically found in apen-injector).

The injection device 1 may be disposable or it may be reusable.

The injection device 1 may provide a fixed dose or a user-settable dose.

The drug or medicament may be contained in a primary package or “drugcontainer” adapted for use with a drug delivery device. The drugcontainer may be, e.g., a cartridge, syringe, reservoir, or other vesselconfigured to provide a suitable chamber for storage (e.g., short- orlong-term storage) of one or more pharmaceutically active compounds. Forexample, in some instances, the chamber may be designed to store a drugfor at least one day (e.g., 1 to at least 30 days). In some instances,the chamber may be designed to store a drug for about 1 month to about 2years. Storage may occur at room temperature (e.g., about 20° C.), orrefrigerated temperatures (e.g., from about −4° C. to about 4° C.). Insome instances, the drug container may be or may include a dual-chambercartridge configured to store two or more components of a drugformulation (e.g., a drug and a diluent, or two different types ofdrugs) separately, one in each chamber. In such instances, the twochambers of the dual-chamber cartridge may be configured to allow mixingbetween the two or more components of the drug or medicament prior toand/or during dispensing into the human or animal body. For example, thetwo chambers may be configured such that they are in fluid communicationwith each other (e.g., by way of a conduit between the two chambers) andallow mixing of the two components when desired by a user prior todispensing. Alternatively or in addition, the two chambers may beconfigured to allow mixing as the components are being dispensed intothe human or animal body.

The drug delivery devices and drugs described herein can be used for thetreatment and/or prophylaxis of many different types of disorders.Exemplary disorders include, e.g., diabetes mellitus or complicationsassociated with diabetes mellitus such as diabetic retinopathy,thromboembolism disorders such as deep vein or pulmonarythromboembolism. Further exemplary disorders are acute coronary syndrome(ACS), angina, myocardial infarction, cancer, macular degeneration,inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis.

Exemplary drugs for the treatment and/or prophylaxis of diabetesmellitus or complications associated with diabetes mellitus include aninsulin, e.g., human insulin, or a human insulin analogue or derivative,a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptoragonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4(DPP4) inhibitor, or a pharmaceutically acceptable salt or solvatethereof, or any mixture thereof. As used herein, the term “derivative”refers to any substance which is sufficiently structurally similar tothe original substance so as to have substantially similar functionalityor activity (e.g., therapeutic effectiveness).

Exemplary insulin analogues are Gly(A21), Arg(B31), Arg(B32) humaninsulin (insulin glargine); Lys(B3), Glu(B29) human insulin; Lys(B28),Pro(B29) human insulin; Asp(B28) human insulin; human insulin, whereinproline in position B28 is replaced by Asp, Lys, Leu, Val or Ala andwherein in position B29 Lys may be replaced by Pro; Ala(B26) humaninsulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30)human insulin.

Exemplary insulin derivatives are, for example, B29-N-myristoyl-des(B30)human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoylhuman insulin; B29-N-palmitoyl human insulin; B28-N-myristoylLysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) humaninsulin; B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyhepta¬decanoyl) human insulin. Exemplary GLP-1, GLP-1analogues and GLP-1 receptor agonists are, for example:Lixisenatide/AVE0010/ZP10/Lyxumia,Exenatide/Exendin-4/Byetta/Bydureon/ITCA 650/AC-2993 (a 39 amino acidpeptide which is produced by the salivary glands of the Gila monster),Liraglutide/Victoza, Semaglutide, Taspoglutide, Syncria/Albiglutide,Dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054,Langlenatide/HM-11260C, CM-3, GLP-1 Eligen, ORMD-0901, NN-9924, NN-9926,NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697,DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034. MOD-6030,CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN andGlucagon-Xten.

An exemplary oligonucleotide is, for example: mipomersen/Kynamro, acholesterol-reducing antisense therapeutic for the treatment of familialhypercholesterolemia.

Exemplary DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin,Saxagliptin, Berberine.

Exemplary hormones include hypophysis hormones or hypothalamus hormonesor regulatory active peptides and their antagonists, such asGonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin),Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin,Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

Exemplary polysaccharides include a glucosaminoglycane, a hyaluronicacid, a heparin, a low molecular weight heparin or an ultra-lowmolecular weight heparin or a derivative thereof, ora sulphatedpolysaccharide, e.g. a poly-sulphated form of the above-mentionedpolysaccharides, and/or a pharmaceutically acceptable salt thereof. Anexample of a pharmaceutically acceptable salt of a poly-sulphated lowmolecular weight heparin is enoxaparin sodium. An example of ahyaluronic acid derivative is Hylan G-F 20/Synvisc, a sodiumhyaluronate.

The term “antibody”, as used herein, refers to an immunoglobulinmolecule or an antigen-binding portion thereof. Examples ofantigen-binding portions of immunoglobulin molecules include F(ab) andF(ab')2 fragments, which retain the ability to bind antigen. Theantibody can be polyclonal, monoclonal, recombinant, chimeric,de-immunized or humanized, fully human, non-human, (e.g., murine), orsingle chain antibody. In some embodiments, the antibody has effectorfunction and can fix complement. In some embodiments, the antibody hasreduced or no ability to bind an Fc receptor. For example, the antibodycan be an isotype or subtype, an antibody fragment or mutant, which doesnot support binding to an Fc receptor, e.g., it has a mutagenized ordeleted Fc receptor binding region.

The terms “fragment” or “antibody fragment” refer to a polypeptidederived from an antibody polypeptide molecule (e.g., an antibody heavyand/or light chain polypeptide) that does not comprise a full-lengthantibody polypeptide, but that still comprises at least a portion of afull-length antibody polypeptide that is capable of binding to anantigen. Antibody fragments can comprise a cleaved portion of a fulllength antibody polypeptide, although the term is not limited to suchcleaved fragments. Antibody fragments that are useful in the presentdisclosure include, for example, Fab fragments, F(ab′)2 fragments, scFv(single-chain Fv) fragments, linear antibodies, monospecific ormultispecific antibody fragments such as bispecific, trispecific, andmultispecific antibodies (e.g., diabodies, triabodies, tetrabodies),minibodies, chelating recombinant antibodies, tribodies or bibodies,intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP),binding-domain immunoglobulin fusion proteins, camelized antibodies, andVHH containing antibodies. Additional examples of antigen-bindingantibody fragments are known in the art.

The terms “Complementarity-determining region” or “CDR” refer to shortpolypeptide sequences within the variable region of both heavy and lightchain polypeptides that are primarily responsible for mediating specificantigen recognition. The term “framework region” refers to amino acidsequences within the variable region of both heavy and light chainpolypeptides that are not CDR sequences, and are primarily responsiblefor maintaining correct positioning of the CDR sequences to permitantigen binding. Although the framework regions themselves typically donot directly participate in antigen binding, as is known in the art,certain residues within the framework regions of certain antibodies candirectly participate in antigen binding or can affect the ability of oneor more amino acids in CDRs to interact with antigen.

Exemplary antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).

The compounds described herein may be used in pharmaceuticalformulations comprising (a) the compound(s) or pharmaceuticallyacceptable salts thereof, and (b) a pharmaceutically acceptable carrier.The compounds may also be used in pharmaceutical formulations thatinclude one or more other active pharmaceutical ingredients or inpharmaceutical formulations in which the present compound or apharmaceutically acceptable salt thereof is the only active ingredient.Accordingly, the pharmaceutical formulations of the present disclosureencompass any formulation made by admixing a compound described hereinand a pharmaceutically acceptable carrier.

Pharmaceutically acceptable salts of any drug described herein are alsocontemplated for use in drug delivery devices. Pharmaceuticallyacceptable salts are for example acid addition salts and basic salts.Acid addition salts are e.g. HCl or HBr salts. Basic salts are e.g.salts having a cation selected from an alkali or alkaline earth metal,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1 C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are known to those of skill in thearts.

Pharmaceutically acceptable solvates are for example hydrates oralkanolates such as methanolates or ethanolates.

Those of skill in the art will understand that modifications (additionsand/or removals) of various components of the substances, formulations,apparatuses, methods, systems and embodiments described herein may bemade without departing from the full scope and spirit of the presentdisclosure, which encompass such modifications and any and allequivalents thereof.

1. An apparatus comprising: a data collection device which is attachableto a proximal end of an injection device, the injection device having adosage knob for allowing a dosage of medicament to be set by a user, anda dose delivery button for allowing a user to cause delivery ofmedicament from the injection device, wherein the data collectiondevice: includes a cavity that is configured to receive the proximal endof the injection device, includes features that are configured to matewith one or more external features of the injection device, isconfigured such that, when installed on the injection device, the datacollection device is manipulated by a user in order to effect operationof the injection device, is configured such that, when the datacollection device is rotated by a user during setting of a dosage ofmedicament, the dosage knob also rotates, is configured such thatmovement of the data collection device in a distal direction iscommunicated to movement of the dose delivery button of the injectiondevice in the distal direction, includes a sensor arrangement which isconfigured to detect rotation of the dosage knob relative to the dosedelivery button when a dose is being delivered, and includes a processorarrangement that is configured to, based on said detected rotation ofthe dosage knob relative to the dose delivery button when the dose isbeing delivered, determine an amount of medicament amount expelled bythe injection device.
 2. The apparatus as claimed in claim 1, whereinthe data collection device is configured to fit closely around the dosedelivery button of the injection device.
 3. The apparatus as claimed inclaim 1, wherein the data collection device has formations thatcooperate with formations on the dosage knob of the injection device. 4.The apparatus as claimed in claim 3, wherein, when the data collectiondevice is placed over the dosage knob of the injection device, theformations on the dosage knob fall between the formations of the datacollection device.
 5. The apparatus as claimed in claim 1, wherein theinjection device is configured such that, once the dose delivery buttonhas moved enough to permit dose delivery, the dosage knob rotatesrelative to the dose delivery button as the dose delivery button ismoved in the distal direction by action of the user.
 6. The apparatus asclaimed in claim 1, wherein the data collection device includes a powersource.
 7. The apparatus as claimed in claim 6, wherein the power sourceis a battery.
 8. The apparatus as claimed in claim 6, wherein the powersource is a coin cell.
 9. The apparatus as claimed in claim 1, whereinthe data collection device contains a printed circuit board.
 10. Theapparatus as claimed in claim 9, wherein during dialing, electroniccomponents on the printed circuit board are not powered.
 11. Theapparatus as claimed in claim 1, wherein the data collection deviceincludes a switch that is configured to be operated upon movement of thedata collection device in the distal direction.
 12. The apparatus asclaimed in claim 11, wherein the data collection device is configured touse operation of the switch to trigger powering of components of thedata collection device
 13. The apparatus as claimed in claim 1, whereinthe data collection device is configured to transmit information using awireless communications link.
 14. An apparatus, comprising: a medicamentadministration apparatus comprising: an injection device having a dosageknob for allowing a dosage of medicament to be set by a user, and a dosedelivery button for allowing a user to cause delivery of medicament fromthe injection device; and a data collection device, wherein the datacollection device is attachable to a proximal end of an injectiondevice, the injection device having a dosage knob for allowing a dosageof medicament to be set by a user, and a dose delivery button forallowing a user to cause delivery of medicament from the injectiondevice, wherein the data collection device: includes a cavity that isconfigured to receive the proximal end of the injection device, includesfeatures that are configured to mate with one or more external featuresof the injection device, is configured such that, when installed on theinjection device, the data collection device is manipulated by a user inorder to effect operation of the injection device, is configured suchthat, when the data collection device is rotated by a user duringsetting of a dosage of medicament, the dosage knob also rotates, isconfigured such that movement of the data collection device in a distaldirection is communicated to movement of the dose delivery button of theinjection device in the distal direction, includes a sensor arrangementwhich is configured to detect rotation of the dosage knob relative tothe dose delivery button when a dose is being delivered, and includes aprocessor arrangement that is configured to, based on said detectedrotation of the dosage knob relative to the dose delivery button whenthe dose is being delivered, determine an amount of medicament amountexpelled by the injection device.
 15. The apparatus as claimed in claim14, wherein the data collection device is configured to fit closelyaround the dose delivery button of the injection device.
 16. Theapparatus as claimed in claim 14, wherein the data collection device hasformations that cooperate with formations on the dosage knob of theinjection device.
 17. The apparatus as claimed in claim 16, wherein,when the data collection device is placed over the dosage knob of theinjection device, the formations on the dosage knob fall between theformations of the data collection device.
 18. The apparatus as claimedin claim 14, wherein the injection device is configured such that, oncethe dose delivery button has moved enough to permit dose delivery, thedosage knob rotates relative to the dose delivery button as the dosedelivery button is moved in the distal direction by action of the user.19. The apparatus as claimed in claim 14, wherein the data collectiondevice includes a switch that is configured to be operated upon movementof the data collection device in the distal direction.
 20. The apparatusas claimed in claim 14, wherein the data collection device is configuredto use operation of the switch to trigger powering of components of thedata collection device.